7-105041015-AG-A

Position:

• chr7-105041015-AG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_182931.3(KMT2E):​c.65del​(p.Gly22ValfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KMT2E NM_182931.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 10.0

Genes affected

KMT2E (HGNC:18541): (lysine methyltransferase 2E (inactive)) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a protein with an N-terminal PHD zinc finger and a central SET domain. Overexpression of the protein inhibits cell cycle progression. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-105041015-AG-A is Pathogenic according to our data. Variant chr7-105041015-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1098297.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-105041015-AG-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2E	NM_182931.3	c.65del	p.Gly22ValfsTer7	frameshift_variant	3/27	ENST00000311117.8	NP_891847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2E	ENST00000311117.8	c.65del	p.Gly22ValfsTer7	frameshift_variant	3/27	1	NM_182931.3	ENSP00000312379	P4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

O'Donnell-Luria-Rodan syndrome Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics, Cologne University

Apr 28, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-104681462;